The goal of this proposal is to investigate mechanisms by which adrenergic blockade or denervation influence ventricular arrhythmias produced by myocardial ischemia in the dog. Specifically, this plan will study effects of not only sympathetic denervation and beta-1 blockade but also alpha blockade on the electrophysiology of ischemic myocardium and associated arrhythmias. In addition, this plan will separately study the effects of local withdrawal of sympathetic influence limited to the ischemic region and compare them with effects of systemic withdrawal of sympathetic influences with all attendant cardiovascular changes. I have previously adapted a technique of regional cardiac denervation produced by phenol to study sympathetic neural control of normal ventricular electrophysiologic properties. In this proposal I will utilize this technique and methods for production of regional cardiac alpha and beta-1 blockade to examine direct mechanisms of sympathetic influence on ischemic electrophysiology independent of systemic cardiovascular alterations. I will study 24-hour and 14 day old myocardial ischemia. Multipolar electrodes will be inserted near the origin of ventricular tachycardia (epicardial mapping). Tachycardia rate, electrogram activation time, and ease of termination and induction will be determined. I will also measure electrogram duration and QT interval and strength interval curves during ventricular pacing. Measurements will be repeated after one of the following: Phentolamine injection into the coronary artery of the ischemic region, intravenous phentolamine, metoprolol injection into the coronary of the ischemic region, intravenous metoprolol, regional sympathetic denervation produced by phenol and stellate ganglionectomy. Effects of drugs injected into the occluded coronary will be validated in each dog by injections of methylene blue and radiolabeled microspheres. By contrasting effects of regional and systemic sympathetic denervation or blockade, it can be determined whether direct effects on the ischemic zone alone or the further indirect effects of systemic denervation or blockade protect from ventricular arrhythmias associated with myocardial ischemia.